1. Field of the Invention
The present invention relates to a method for fabricating hydrogel particles having an accurately controlled size using liposomes.
2. Description of the Background
Liposomes may be generally defined as closed vesicles having a lipid membrane surrounding an entrapped aqueous core. They may be either unilamellar vesicles having a single membrane layer or multilamellar vesicles having multiple membrane layers.
Liposomes have been used in a variety of commercial applications, and for encapsulating a variety of different agents therein. For example, liposomes have been used as a delivery vehicle for the sustained release of drugs both in parental and topical applications. It is known that liposomes may be targeted to specific cells in the body when used in association with immunoglobulins raised against the target cells.
Liposomes have been fabricated using a number of different lipid formulations and methods depending upon the specific intended use. Further, methods are known for producing liposomes of a particular size and wall thickness. For example, such methods have included the use of hydrodynamic shear, U.S. Pat. No. 5,082,664, reverse phase evaporation, U.S. Pat. No. 4,235,571, sonication, U.S. Pat. No. 4,089,801, detergent dialysis and extrusion through a membrane pores, U.S. Pat. No. 5,008,050. In these methods, the lipid compositions used are chosen based upon properties related to solution dynamics, such as aggregation and fusion, or controlled release, such as release of encapsulated agents.
Hydrogels are polymers which contain chemical constituents having a high water content and high viscosity. These materials are used, for example, as fillers in the food industry, as biomaterials for use in contact lens material and as controlled release matrices, for example. One example is cross-linked polyethylene oxide which absorbs up to 100 times its weight of water, which can be released when desired. Another example of a hydrogel is the alginates, which are high molecular weight oligosaccharides derived from algae. At present, alginate hydrogel particles are fabricated using methods which involve drops formed as an alginate solution is extruded from a needle or sprayed from a nozzle. These generally result in particles having a size range of from 0.5 to 10 mm. Unfortunately, however, it is presently difficult to accurately control the size of such particles in large scale. For example, both of U.S. Pat. Nos. 4,520,178 and 4,192,900 describe methods of producing hydrogel particles, but neither of the methods described therein afford hydrogel particles in the submicron range with the same unimodal distribution of size. Also, neither of these methods affords particles which are surrounded by a lipid bilayer. Thus, although hydrogel reactions in liposomes have been conducted, the particles formed are not formed in liposomes of unimodal submicron size, nor do they involve hydrogel reactions which rely on transporting the initiator of the reaction across the liposome bilayer.
It would be extremely desirable, however, if a method for fabricating hydrogel particles were known wherein very accurate control of the hydrogel particle size could be obtained. This would allow for the release of chemicals, drugs or other materials therefrom in a very controlled manner.